During the last year the EM lab has collaborated with labs in CBER and CDER in studies related to product safety. A) In experiments designed to simulate the activation of latent retroviruses, cells of monkey and mouse origin were treated for various times with agents known to induce viral replication. Cultures were subsequently examined by TEM for the presence of retroviral particles. An increase in both C-type and A-type retroviruses was seen in the treated murine cells. (With A. Khan & J. Sears, CBER, DVP) B) Coronary damage has been observed following the use of a Type-III phosphodiesterase inhibitor. The mechanism of this pathology was investigated in tissue samples from rats exposed to a single s.c. injection of inhibitor. TEM examination revealed degenerative changes in vascular endothelial and smooth muscle cells suggesting that endothelial cell injury may play a critical role in the pathologic process. (With Dr. J. Zhang, CDER, Div. Of Applied Pharmacology Research). The EM lab is also participating in a research project related to vaccine development with Dr. I. Berkower (CBER, DVP). The goal of these studies is to enhance the immunologic response to HIV by creating novel multimeric hybrid particles containing the HIV gp 120 envelope molecule. After isolation and purification, the assembly of the hybrids into stable multimeric particles is assessed by TEM using negative staining. The EM lab has entered into an InterAgency Agreement with the Cell Biology lab of NCI for the study of melanomas, melanocyte physiology, and melanocyte-keratinocyte interactions. (With V. Hearing & V. Virador)